It has been established that the functioning of the sympathetic division of the autonomic nervous system can be altered by the presence of obesity or by weight change. Measures have been made of catecholamine levels in the plasma and urine as well as electrical activity in the peroneal nerve. By a combination of spectral analysis of heart rate variability and measures of heart rate following selective blockades with anti-sympathetic and anti-parasympathetic agents, it has been possible to make reproducible determinations of both sympathetic and parasympathetic activity as affecting heart rate. The generalizability of these findings to other portions of the autonomic nervous system is suggested by the demonstration that weight changes cause alterations both in sympathetic and parasympathetic balance as measured by changes in heart rate variability. We propose to utilize this method to study the effect of leptin on autonomic activity. Since leptin may control body fat storage not only by alterations of food intake but also energy outgo, the role of the autonomic nervous system in overall change in energy metabolism becomes important to observe. To this end, measures of autonomic activity after leptin administration will be made. Furthermore, agents which permit rapid blockade of the sympathetic and parasympathetic divisions without some of the adverse symptoms of administration of large doses of atropine, will be investigated.